Endocrine Pancreas (Diabetes)

Diabetes mellitus is a group of metabolic disorders characterized by chronic hyperglycemia, which results from defects in insulin secretion, insulin action, or both. This pressbook will explore the histological features of both type 1 diabetes and type 2 diabetes, as well as the complications that arise due to chronic hyperglycemia.

ENDOCRINE PANCREAS AND ISLETS OF LANGERHANS:

The pancreas has both exocrine and endocrine functions. The endocrine pancreas consists of clusters of cells known as the Islets of Langerhans (images below), which are responsible for producing important hormones that regulate blood sugar:

• Beta cells: Produce insulin (about 75% of islet cells).
• Alpha cells: Secrete glucagon (about 20% of islet cells).
• Delta cells: Release somatostatin, which inhibits the secretion of both insulin and glucagon.
• Gamma cells: Produce pancreatic polypeptide.
• Epsilon cells: Secrete ghrelin, which regulates hunger.

In both type 1 and type 2 diabetes, the islets undergo pathological changes that impair insulin regulation.

PATHOLOGY OF TYPE 1 DIABETES:

Type 1 diabetes is characterized by autoimmune destruction of the beta cells in the pancreas, leading to a lack of insulin production. The main histological feature of type 1 diabetes is insulitis, which is the infiltration of the islets by lymphocytes. This immune-mediated attack eventually leads to the destruction of the beta cells, resulting in an absolute insulin deficiency.

• Histology: Lymphocytic infiltration in and around the islets, which can be seen under a microscope as small, round dark cells surrounding the islet tissue.

• Clinical Relevance: The destruction of beta cells leads to symptoms of hyperglycemia, and patients with type 1 diabetes require insulin replacement therapy.

PATHOLOGY OF TYPE 2 DIABETES:

Type 2 diabetes is characterized by insulin resistance and a relative lack of insulin production. Over time, beta-cell function deteriorates, and histological changes can be observed in the pancreatic islets.

• Histology: A hallmark of type 2 diabetes is the accumulation of amyloid (abnormal protein deposits) in the islets. Amyloid deposition is associated with beta-cell dysfunction and eventual beta-cell loss.

• Clinical Relevance: As beta-cell function declines, patients with type 2 diabetes may eventually require medications that increase insulin sensitivity or even insulin therapy.

COMPLICATIONS OF DIABETES: 

Chronic hyperglycemia in diabetes leads to significant complications affecting multiple organ systems:

• Diabetic Nephropathy: Hyperglycemia causes damage to the kidneys’ small blood vessels, leading to glomerular damage. A classic histological feature is nodular glomerulosclerosis (Kimmelstiel-Wilson nodules), which involves the thickening of the glomerular basement membrane and increased mesangial matrix.
  • Histology: Thickened blood vessels and nodules within the glomeruli.

• Diabetic Retinopathy: Damage to the small blood vessels in the retina can cause vision loss due to micro-aneurysms, hemorrhages, and the formation of new, fragile blood vessels (neo-vascularization).
  • Histology: Thickened capillary walls and proliferation of new blood vessels.

• Atherosclerosis: Diabetes accelerates the development of atherosclerosis, leading to the thickening and hardening of large arteries. This results in an increased risk of heart attacks, strokes, and peripheral artery disease.
  • Histology: Plaque buildup and narrowing of the arterial walls.

• Peripheral Arterial Disease and Neuropathy: Reduced blood flow to the extremities, combined with nerve damage (neuropathy), leads to ulcers, infections, and, in severe cases, amputation.
  • Histology: Thickened arterial walls and loss of myelin sheaths in peripheral nerves.